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微小RNA-675-5p促进缺氧诱导的结肠癌细胞上皮-间质转化。

MiR-675-5p supports hypoxia induced epithelial to mesenchymal transition in colon cancer cells.

作者信息

Costa Viviana, Lo Dico Alessia, Rizzo Aroldo, Rajata Francesca, Tripodi Marco, Alessandro Riccardo, Conigliaro Alice

机构信息

Innovative Technological Platforms for Tissue Engineering, Theranostic and Oncology, Rizzoli Orthopedic Institute, Palermo, Italy.

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy.

出版信息

Oncotarget. 2017 Apr 11;8(15):24292-24302. doi: 10.18632/oncotarget.14464.

DOI:10.18632/oncotarget.14464
PMID:28061476
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5421847/
Abstract

The survival rates in colon cancer patients are inversely proportional to the number of lymph node metastases. The hypoxia-induced Epithelial to Mesenchymal Transition (EMT), driven by HIF1α, is known to be involved in cancer progression and metastasis. Recently, we have reported that miR-675-5p promotes glioma growth by stabilizing HIF1α; here, by use of the syngeneic cell lines we investigated the role of the miR-675-5p in colon cancer metastasis.Our results show that miR-675-5p, over expressed in metastatic colon cancer cells, participates to tumour progression by regulating HIF1α induced EMT. MiR-675-5p increases Snail transcription by a dual strategy: i) stabilizing the activity of the transcription factor HIF1α and ii) and inhibiting Snail's repressor DDB2 (Damage specific DNA Binding protein 2).Moreover, transcriptional analyses on specimens from colon cancer patients confirmed, in vivo, the correlation between miR-675-5p over-expression and metastasis, thus identifying miR-675-5p as a new marker for colon cancer progression and therefore a putative target for therapeutic strategies.

摘要

结肠癌患者的生存率与淋巴结转移数量呈负相关。已知由缺氧诱导因子1α（HIF1α）驱动的上皮-间质转化（EMT）参与癌症进展和转移。最近，我们报道了miR-675-5p通过稳定HIF1α促进胶质瘤生长；在此，我们利用同基因细胞系研究了miR-675-5p在结肠癌转移中的作用。我们的结果表明，在转移性结肠癌细胞中高表达的miR-675-5p通过调节HIF1α诱导的EMT参与肿瘤进展。miR-675-5p通过双重策略增加Snail转录：i）稳定转录因子HIF1α的活性；ii）抑制Snail的抑制因子损伤特异性DNA结合蛋白2（DDB2）。此外，对结肠癌患者标本的转录分析在体内证实了miR-675-5p过表达与转移之间的相关性，从而确定miR-675-5p为结肠癌进展的新标志物，因此是治疗策略的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/5421847/48399cd4ca7d/oncotarget-08-24292-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/5421847/940de4cc6d2c/oncotarget-08-24292-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/5421847/4a21eaf91194/oncotarget-08-24292-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/5421847/83963ee53b62/oncotarget-08-24292-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/5421847/9a2f4c8dcada/oncotarget-08-24292-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/5421847/48399cd4ca7d/oncotarget-08-24292-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/5421847/940de4cc6d2c/oncotarget-08-24292-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/5421847/4a21eaf91194/oncotarget-08-24292-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/5421847/83963ee53b62/oncotarget-08-24292-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/5421847/9a2f4c8dcada/oncotarget-08-24292-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/5421847/48399cd4ca7d/oncotarget-08-24292-g005.jpg

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